Chemosensor ensemble with selectivity for inositol-trisphosphate
Chemosensor ensemble with selectivity for inositol-trisphosphate
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DOI：
10.1021/ja980990c
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发表时间：
1998-08-26
影响因子：
15
通讯作者：
Anslyn, EV
中科院分区：
文献类型：
--
作者：
Niikura, K;Metzger, A;Anslyn, EV
用于生物活性分子的光学传感器的发展使人们能够在细胞过程中监测分析物。1例如，已经开发出非常有效的传感器，用于在细胞信号传导事件期间对Ca 2+进行全细胞成像。2a，B此外，毛细管电泳（CE）已用于提取和分析pL量的细胞质。2c一个感兴趣的分子是聚阴离子第二信使肌醇-1，4，5-三磷酸盐（IP 3）。3然而，由于IP 3没有发色团，这种分析尚未完成。在开发对IP 3具有选择性的化学传感器时，可以考虑将许多结构基序用于传感器的受体部分。水中阴离子的合成受体通常分为四类：大环多铵/胍，4裂，5环番/杯芳烃，6和卟啉/sapphyrin。大环聚铵受体通常具有最高的亲和力，但操纵其识别选择性通常限于改变空腔大小。裂缝基序具有优势，因为形状固有地更通用，但是很少（如果有的话）这样的受体在质子介质中显示出阴离子客体的强结合。IP 3的细胞内浓度通常在纳摩尔范围内，开发IP 3传感器需要强结合。8在此，我们报道了一种裂缝样受体，当与光学信号分子配对时，可用于定量纳摩尔浓度的IP 3。尽管天然IP 3受体位点的结构尚未阐明，但精氨酸修饰试剂阻断IP 3结合，9从而表明胍基可能是自然界中IP 3的基本识别元件。因此，我们专注于在我们的合成受体中使用胍。10位阻齿轮11用于赋予六个胍盐朝向腔体内部（1a）取向的偏好。
The development of optical sensors for biologically active molecules gives one the ability to monitor analytes during cellular processes. 1 For example, very effective sensors for the whole cell imaging of Ca2+ during cellular signaling events have been developed. 2a, b In addition, capillary electrophoresis (CE) has been used to extract and analyze pL quantities of cytoplasm. 2c One molecule that would be of interest to monitor by using CE is the polyanionic second messenger inositol-1, 4, 5-trisphosphate (IP3). 3 However, because IP3 does not have a chromophore, such an analysis has not yet been accomplished. In the development of a chemosensor with selectivity for IP3, a number of structural motifs can be considered for the receptor portion of the sensor. Synthetic receptors for anions in water typically fall into four categories: macrocyclic polyammoniums/guanidiniums, 4 clefts, 5 cyclophanes/calixarenes, 6 and porphyrins/sapphyrins. 7 The macrocyclic polyammonium receptors generally have the highest affinities, but manipulating their recognition selectivity is often limited to varying the cavity size. A cleft motif has an advantage since the shape is inherently more versatile, but few if any such receptors show strong binding of anionic guests in protic media. Strong binding is required for the development of a sensor for IP3, whose intracellular concentration is typically in the nanomolar range. 8 Herein we report a cleft-like receptor that, when paired with an optical signaling molecule, can be used to quantitate IP3 at nanomolar concentrations.Although the structures of the natural IP3 receptor sites have not been elucidated, arginine-modifying reagents block IP3 binding, 9 thereby suggesting that guanidinium groups may be essential recognition elements for IP3 in nature. We therefore focused upon the use of guanidiniums in our synthetic receptor. 10 Steric gearing11 was used to impart a preference for six guanidiniums to be oriented toward the interior of a cavity (1a).